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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proteomic screening of variola virus reveals a unique NF-kB inhibitor that is highly conserved among pathogenic orthopoxviruses
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Proteomic screening of variola virus reveals a unique NF-kB inhibitor that is highly conserved among pathogenic orthopoxviruses

机译:对天花病毒的蛋白质组学筛选显示出独特的NF-kB抑制剂,在病原性正痘病毒中高度保守

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摘要

Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein-protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-kB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-kB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.
机译:病毒和宿主蛋白之间的二元相互作用的鉴定已成为研究病毒的向性和致病性的有价值的工具。在这里,我们介绍了通过使用针对各种人类cDNA文库的酵母2杂交筛选对独特的天花病毒蛋白质组进行的第一个系统蛋白质相互作用筛选。鉴定了几种蛋白质-蛋白质相互作用,包括天花G1R,含ankryin / F-box的蛋白质和人类核因子kappa-B1(NF-kB1)/ p105之间的相互作用。这代表了病原体编码蛋白和NF-kB1 / p105之间的首次直接相互作用。 G1R的直系同源物存在于多种致病性正痘病毒中,但在牛痘病毒中却不存在,这些病毒蛋白中任何一种的表达均可阻断人细胞中的NF-kB信号传导。因此,对天花病毒的蛋白质组学筛选具有发现人类先天性抗病毒反应调节剂的潜力。

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  • 作者单位

    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610;

    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610;

    Myriad Genetics, Salt Lake City, UT 84108;

    Myriad Genetics, Salt Lake City, UT 84108;

    Myriad Genetics, Salt Lake City, UT 84108;

    Myriad Genetics, Salt Lake City, UT 84108;

    Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2S2;

    Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2S2;

    Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2S2;

    World Health Organization Collaborating Center for Smallpox and other Poxvirus Infections, Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;

    World Health Organization Collaborating Center for Smallpox and other Poxvirus Infections, Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;

    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    ankyrin repeats; Skp1; yeast 2-hybrid;

    机译:锚蛋白重复;Skp1;酵母2杂种;

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